Animal models of anti-neutrophil cytoplasmic antibody associated vasculitis

Abstract

Anti-neutrophil cytoplasmic antibodies (ANCA) are a group of auto-antibodies directed against components of neutrophil granules and monocyte lysosomes. Since the first description of ANCA by Davies et al in 1982 in patients with segmental necrotizing glomerulonephritis, ANCA have been demonstrated in a number of primary vasculitic syndromes1. In 1985, van der Woude et al reported on ANCA as a specific and sensitive marker for active Wegener's granulomatosis2. ANCA were later shown to be present in Churg-Strauss syndrome3,4, microscopic polyangiitis5, and pauci-immune necrotizing crescentic glomerulonephritis (NCGN)6,7. In most cases of systemic vasculitis, the primary target antigens for ANCA are proteinase 3 (Pr3), a serine proteinase, and myeloperoxidase (MPO), an enzyme involved in the production of reactive oxygen intermediates6,8,9,10. Both enzymes are present in secretory granules of neutrophils and monocytes. Although anti-Pr3 and anti-MPO are found across the spectrum of ANCA-associated vasculitides, it is now well established that anti-Pr3 is a sensitive marker for Wegener's granulomatosus whereas anti-MPO is predominantly found in microscopic polyangiitis, pauci-immune NCGN, and Churg-Strauss syndrome11. Although not uniformly accepted, changes in titers of ANCA seem to reflect changes in disease activity12,13,14,15,16.